Composition and method for compounded therapy

ABSTRACT

A compounded transdermal cream for topical administration of a compounded therapy includes a nerve depressant such as gabapentin in an amount between approximately 5% and 15% by weight of the transdermal cream, an NSAID (Non-Steroidal Anti-Inflammatory Drug) such as nabumetone in an amount between approximately 5% and approximately 25% by weight of the transdermal cream, a tricyclic antidepressant such as amitriptyline in an amount between approximately 0.5% and approximately 4% by weight of the transdermal cream, a local anesthetic such as lidocaine and prilocaine in an amount between approximately 1% and approximately 7% by weight of the transdermal cream, and dimethyl sulfoxide (DMSO).

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation in-part of co-pending U.S.patent application Ser. No. 13/448,088, entitled Composition and Methodfor Compounded Therapy, filed Apr. 16, 2012, which is a continuation ofU.S. patent application Ser. No. 13/409,738, entitled Composition andMethod for Compounded Therapy, filed Mar. 1, 2012, now abandoned, whichis a continuation-in-part of U.S. patent application Ser. No.13/337,598, entitled Composition and Method for Compounded Therapy,filed Dec. 27, 2011, now abandoned.

FIELD OF THE INVENTION

The present application relates to compounded therapies. In particular,the present application relates to compositions for compounded therapyand methods of compounding medications.

BACKGROUND

Transdermal creams are employed to deliver medication to the skin of apatient. Conventional compositions intended for topical administrationinclude EMLA cream, a eutectic mixture of lidocaine and prilocaine in anemulsified topical cream, such as disclosed by U.S. Pat. Nos. 6,299,902and 4,562,060, which are incorporated herein by reference in theirentireties. However, conventional transdermal creams may include variousdrawbacks, such as addressing limited medical conditions, creatingadverse side effects, and/or having limited shelf lives. Additionally,conventional methods of manufacturing transdermal creams may beinefficient and/or lack precision with the amount of active ingredients,or have other drawbacks.

SUMMARY

The present embodiments may relate to topically delivered compoundedmedications for treatment of various ailments, such as pain,osteoarthritis, epilepsy, inflammation, muscle fatigue, spasms, and/orother ailments. In one aspect, a transdermal cream for the effectiveadministration of multiple medications simultaneously for one or moreailments may be provided. The transdermal cream may include lowconcentrations of lidocaine, prilocaine, meloxicam, and lamotrigineand/or topiramate. Alternatively, the transdermal cream may include abase having lidocaine and prilocaine to which is added a fine powder ofone or more medications. The medication in powder form may be generatedfrom grinding up tablets of NSAIDs (Non-Steroidal Anti-InflammatoryDrugs), nerve depressants, anticonvulsants, antidepressants, musclerelaxants, anesthetics, and/or other active ingredients. The presentembodiments also relate to methods of making the compositions discussedherein.

In one aspect, a compounded transdermal cream for topical administrationof a compounded therapy includes a nerve depressant such as gabapentinin an amount between approximately 5% and 15% by weight of thetransdermal cream. The compounded transdermal cream may also include anNSAID (Non-Steroidal Anti-Inflammatory Drug) such as nabumetone in anamount between approximately 5% and approximately 25% by weight of thetransdermal cream. The compounded transdermal cream may also include atricyclic antidepressant such as amitriptyline in an amount betweenapproximately 0.5% and approximately 4% by weight of the transdermalcream. The compounded transdermal cream may also include a localanesthetic such as lidocaine and prilocaine in an amount betweenapproximately 1% and approximately 7% by weight of the transdermalcream. The compounded transdermal cream may also include dimethylsulfoxide (DMSO).

In one formulation, the gabapentin may be present in an amountapproximately 6% by weight of the transdermal cream, the nabumetone maybe present in an amount approximately 10% by weight of the transdermalcream, the amitriptyline may be present in an amount approximately 2% byweight of the transdermal cream, and the lidocaine and prilocaine mayeach be present in an amount approximately 1.5% by weight of thetransdermal cream. The DMSO may be present in an amount approximately20% by weight of the transdermal cream. A thickening agent may also bepresent in an amount approximately 2% by weight of the transdermalcream.

In another aspect, a compounded transdermal cream includes gabapentin inan amount approximately 6% by weight of the transdermal cream,nabumetone in an amount approximately 10% by weight of the transdermalcream, amitriptyline in an amount approximately 2% by weight of thetransdermal cream, lidocaine and prilocaine cream (2.5%/2.5%) in anamount approximately 60% by weight of the transdermal cream such thatthe transdermal cream comprises lidocaine in an amount approximately1.5% by weight of the transdermal cream and prilocaine in an amountapproximately 1.5% by weight of the transdermal cream, dimethylsulfoxide (DMSO) in an amount approximately 20% by weight of thetransdermal cream, and a thickening agent in an amount approximately 2%by weight of the transdermal cream.

In yet another aspect, a method of compounding a transdermal creamincludes wetting a plurality of dry powder active agents with dimethylsulfoxide (DMSO) and mixing the wetted dry powder active agents with alidocaine and prilocaine cream (2.5%/2.5%). The dry powder active agentsmay include gabapentin, nabumetone, and amitriptyline. The gabapentinmay be present in the transdermal cream in an amount betweenapproximately 5.0% and 15.0% by weight of the transdermal cream. Thenabumetone may be present in an amount of between approximately 5.0% andapproximately 25% by weight of the transdermal cream. The amitriptylinemay be present in an amount between approximately 0.5% and approximately4.0% by weight of the transdermal cream.

In one formulation, the gabapentin may be present in an amountapproximately 6% by weight of the transdermal cream, the nabumetone maybe present in an amount approximately 10% by weight of the transdermalcream, the amitriptyline may be present in an amount approximately 3% byweight of the transdermal cream, and the lidocaine and prilocaine mayeach be present in an amount approximately 1.5% by weight of thetransdermal cream. The DMSO may be present in an amount approximately20% by weight of the transdermal cream. The method may further includeadding a thickening agent to the lidocaine and prilocaine cream(2.5%/2.5%) before or after mixing the wetted dry powder activeingredients with the lidocaine and prilocaine cream (2.5%/2.5%). Thethickening agent may be present in an amount approximately 2% by weightof the transdermal cream.

The above-described and other features and advantages of the presentdisclosure will be appreciated and understood by those skilled in theart from the following detailed description, drawings, and appendedclaims.

BRIEF DESCRIPTION OF THE DRAWINGS

There is shown in the drawings embodiments which are presentlypreferred, it being understood, however, that the invention can beembodied in other forms without departing from the spirit or essentialattributes thereof.

FIG. 1 depicts an exemplary method of compounding; and

FIG. 2 depicts another exemplary method of compounding.

DETAILED DESCRIPTION OF THE INVENTION

The present embodiments may relate to topically delivered compoundedmedications for treatment of various ailments, such as pain,osteoarthritis, epilepsy, inflammation, muscle fatigue, spasms, and/orother ailments. In one aspect, a transdermal cream for the effectiveadministration of multiple medications simultaneously for one or moreailments may be provided. The transdermal cream may include lowconcentrations of lidocaine, prilocaine, meloxicam, lamotrigine and/ortopiramate, and other active ingredients.

Alternatively, the transdermal cream may include a base having bothlidocaine and prilocaine, and to which is added a fine powder of one ormore medications. The medication in fine powder form may be generatedfrom grinding up tablets of NSAIDs (Non-Steroidal Anti-InflammatoryDrugs), anticonvulsants, nerve depressants, muscle relaxants, NMDA(N-Methyl-D-aspartate) receptor antagonists, opiate or opioid agonists,antidepressants, and/or other active agents. The fine powder may allowfor precise amounts of the active ingredients to be added to the base.The transdermal cream may exhibit excellent storage characteristics, andavoid separation and/or degradation of the active ingredients from thebase for substantial lengths of time.

In one aspect, a transdermal cream may include lidocaine in an amountbetween approximately 0.5% and approximately 7.0% by weight of thetransdermal cream; prilocaine in an amount between approximately 0.5%and approximately 7.0% by weight of the transdermal cream; meloxicam inan amount between approximately 0.01% and approximately 5.0% by weightof the transdermal cream; and lamotrigine and/or topiramate in an amountbetween approximately 0.5% and approximately 5.0% by weight of thetransdermal cream. As a result, the transdermal cream may allow for thetopical administration of lidocaine, prilocaine, meloxicam, andlamotrigine and/or topiramate simultaneously during use. In oneembodiment, the transdermal cream may comprise approximately 2.0% byweight lidocaine and prilocaine, respectively; approximately 0.09% byweight meloxicam; and approximately 2.5% by weight either lamotrigine ortopiramate.

In another aspect, a method of compounding one or more medications witha transdermal cream for the topical administration of a compoundedtherapy may be provided. The method may include grinding up one or moretablets of a NSAID, an anticonvulsant, a nerve depressant, a musclerelaxant, a NMDA receptor antagonist, antidepressant, and/or an opiateor opioid agonist into a fine powder of medication. The method may alsoinclude adding the fine powder of medication to a transdermal creamcontaining both lidocaine and prilocaine, the transdermal creamincluding both lidocaine and prilocaine in an amount of betweenapproximately 0.5% and approximately 7.0% by weight of the transdermalcream. The method may include adding the fine powder of medication tothe transdermal cream in a sufficient amount such that the transdermalcream includes the medication that is ground up in an amount of betweenapproximately 0.01% and approximately 5.0% by final weight of thetransdermal cream.

The fine powder may be a fine powder of compounded medication thatincludes two or more active ingredients. For example, the activeingredients may comprise a NSAID, such as meloxicam, and a nervedepressant or an anticonvulsant, such as lamotrigine and/or topiramate.In one embodiment, an amount of ground up compounded medication is addedto the base such that the final composition of the transdermal creamafter the fine powder of compounded medication is added is approximately2.0% by weight lidocaine, approximately 2.0% by weight prilocaine,approximately 0.09% by weight meloxicam, and approximately 2.5% byweight either lamotrigine or topiramate.

I. Compositions for Compounded Therapy

The present embodiments may relate to a compounded medication program.The compounded medication program may address several ailmentssimultaneously. In one aspect, the present embodiments may be intendedto intended to minimize skin damage or irritation caused by the topicaladministration of various medications. Administering low doses orapplying transdermal creams or gels with low concentrations of one ormore active ingredients may minimize adverse side effects, such as sideeffects that develop with prolonged usage.

For instance, Stevens-Johnson Syndrome (SJS) and toxic epidermalnecrolysis (TEN) are two forms of life-threatening skin conditions. SJSis a potentially deadly skin disease that usually results from a drugreaction. Drugs that have been linked to SJS include, but are notlimited to: NSAIDs, allopurinol, phenytoin, carbamazepine, barbiturates,anticonvulsants, and sulfa antibiotics. However, almost any drug(prescription or over-the-counter) could potentially cause SJS if asevere enough allergy is present.

The onset of severe symptoms in drug related SJS may not appear for 1-2weeks after first taking the drug causing the allergic reaction. Initialnon-specific symptoms such as coughing, aching, headaches, fevers,vomiting, and diarrhea are commonly seen. These symptoms are usuallyfollowed by a red rash across the face and trunk of the body, laterfollowed by blisters, and in some situations the nails and hair begin tofall out.

SJS is a very serious and potentially deadly condition and should betreated accordingly. Discontinuation of the medication and treatment ofthe “new infection” with a suitable antibiotic is the first step. Insome situations, a patient is treated in a burn unit if necessary.However, compounded therapies may administer lower doses of activeagents topically, and thus the effect of any adverse skin reaction maybe lowered due to the lower doses of agent that the patient is allergicto.

In view of the foregoing, the present embodiments may include providing,within a base composition, several medications that address differentailments. The medications may be mixed in low concentrations to minimizeany adverse reaction to the topical cream or gel containing the severalmedications.

The medications may be mixed with the base composition for topicaladministration to a patient. The medications may include one or morelocal anesthetics, such as lidocaine, prilocaine, or benzocaine; one ormore NSAIDs, such as meloxicam; and one or more nerve depressants and/oranticonvulsants, such as gabapentin, topiramate, or lamotrigine. Themedications may also include one or more muscle relaxants, such asbaclofen or cyclobenzaprine; one or more NMDA receptor antagonists, suchas ketamine; and/or one or opiate or opioid agonists, such as C2 or C3opiate agonists, or tramadol.

II. Meloxicam/Lamotrigine/Lidocaine/Prilocaine Compounded Medication

In one aspect, a transdermal cream or gel may include lidocaine,prilocaine, meloxicam, and lamotrigine. Lidocaine and prilocaine areamide-type local anesthetic agents. They may come in commerciallyavailable creams.

The amount of lidocaine and prilocaine in the transdermal cream may beapproximately the same. The amount of lidocaine and prilocaine may eachbe between approximately 0.5% and approximately 5.0% of the total weightof the transdermal cream. Alternatively, the amount of lidocaine andprilocaine may each be between approximately 1.0% and approximately 4.0%of the total weight of the transdermal cream, or between approximately1.5% and approximately 3.0% of the total weight of the transdermalcream. In one preferred embodiment, the amount of lidocaine andprilocaine may each be approximately 2.0% of the total weight of thefinal transdermal cream or gel.

Meloxicam is a NSAID that may provide pain relief, such as pain relieffor osteoarthritis or rheumatoid arthritis. In one aspect, the amount ofmeloxicam in the transdermal cream or gel may be less than that of theother active ingredients.

The amount of meloxicam in the transdermal cream may be betweenapproximately 0.01% and approximately 5.0% of the total weight of thetransdermal cream, or between approximately 0.03% and approximately 3.0%of the total weight of the transdermal cream. Preferably, the amount ofmeloxicam may be between approximately 0.05% and approximately 0.15% ofthe total weight of the transdermal cream. In one preferred embodiment,the amount of meloxicam may be approximately 0.09% of the total weightof the transdermal cream or gel.

Lamotrigine may be characterized as an anticonvulsant. It may be used asan antiepileptic drug to treat epilepsy or bi-polar disorders. In oneaspect, the amount of lamotrigine in the transdermal cream or gel may bemore than the other active ingredients, such as lidocaine, prilocaine,meloxicam, and/or other active ingredients.

The amount of lamotrigine in the transdermal cream may be betweenapproximately 0.5% and approximately 5.0% of the total weight of thetransdermal cream, or between approximately 1.5% and approximately 3.5%of the total weight of the transdermal cream. Preferably, the amount oflamotrigine may be between approximately 2.0% and approximately 3.0% ofthe total weight of the transdermal cream. In one preferred embodiment,the amount of lamotrigine may be approximately 2.5% of the total weightof the transdermal cream or gel.

III. Meloxicam/Topiramate/Lidocaine/Prilocaine Compounded Medication

In one aspect, a transdermal cream or gel may include lidocaine,prilocaine, meloxicam, and topiramate. The amounts of lidocaine,prilocaine, and meloxicam may be as stated above. Alternatively, otheramounts of lidocaine, prilocaine, and meloxicam may be used.

Topiramate may be characterized as an antiepileptic drug used to treatepilepsy or migraines. In one aspect, the amount of topiramate in thetransdermal cream or gel may be more than the other active ingredients,such as lidocaine, prilocaine, meloxicam, and/or other activeingredients.

The amount of topiramate in the transdermal cream may be betweenapproximately 0.5% and approximately 5.0% of the total weight of thetransdermal cream, or between approximately 1.5% and approximately 3.5%of the total weight of the transdermal cream. Preferably, the amount oftopiramate may be between approximately 2.0% and approximately 3.0% ofthe total weight of the transdermal cream. In one preferred embodiment,the amount of topiramate may be approximately 2.5% of the total weightof the transdermal cream or gel.

IV. Exemplary Method of Compounding

FIG. 1 depicts an exemplary method of compounding one or moremedications with a transdermal cream or gel 100. The method 100 mayinclude providing a base composition having one or more localanesthetics 102; and adding to the base a fine powder of medicationcomprising: one or more NSAIDs 104; one or more anticonvulsants 106; oneor more or nerve depressants 108; one or more muscle relaxants 110; oneor more NMDA receptor antagonists 112; and/or one or more opiate oropioid agonists 114. The transdermal cream or gel may includeadditional, fewer, or alternate steps and/or ingredients.

The method 100 may comprise providing a base composition 102. The basecomposition may comprise one or more local anesthetics 102. Primaryexamples of local anesthetics that the transdermal creams and basecomposition disclosed herein may employ include, but are not limited to,lidocaine, prilocaine, benzocaine, and/or tetracaine. The localanesthetics may comprise between approximately 0.1% and approximately5.0% by weight of the transdermal cream. Other amounts may be used,including those discussed elsewhere herein. The base composition mayinclude additional, fewer, or alternate ingredients.

Preferably, the base composition may include lidocaine and/orprilocaine. In one embodiment, the base composition may comprise anequal amount of lidocaine and prilocaine, such as between approximately2.0% and approximately 3.0% by weight of the transdermal cream. Otheramounts may be used, including those discussed elsewhere herein.

The method 100 may comprise adding to the base composition a fine powderof medication that includes one or more NSAIDs 104. NSAIDs may decreaseinflammation, swelling, and pain. NSAIDs that may be added to the basecomposition may include: (1) oxicams—meloxicam and piroxicam; (2)salicylic acid derivatives—aspirin, diflunisal, salsalate, andtrilisate; (3) propionic acids—flurbiprofen, ibuprofen, ketoprofen,naproxen, and oxaprozin; (4) acetic acids—diclofenac, etodolac,indomethacin, ketorolac, nabumetone, sulindac, and tolmetin; (5)fenamates—meclofenamate; and/or (6) COX-2 inhibitors—celecoxib,rofecoxib, and valdecoxib. Preferably, the final transdermal cream maycomprise a low concentration of an oxicam, such as meloxicam orpiroxicam, in a low amount between approximately 0.01% and 5.0% byweight of the final transdermal cream. In one embodiment, the finaltransdermal cream may include approximately 0.09% meloxicam by weight.Other amounts may be used, including those discussed elsewhere herein.

The method 100 may comprise adding to the base composition a fine powderof medication that includes one or more anticonvulsants 106.Anticonvulsants that may be added to the base composition may includelamotrigine and/or topiramate. The final transdermal cream may includean anticonvulsant in a low amount between approximately 0.1% andapproximately 5.0% by weight of the final transdermal cream. Preferably,the final transdermal cream may comprise approximately 2.5% of eitherlamotrigine or topiramate by weight. Other amounts may be used,including those discussed elsewhere herein.

The method 100 may comprise adding to the base composition a fine powderof medication that includes one or more nerve depressants 108. Nervedepressants that may be added to the base composition may includegabapentin and/or others. The low amount of nerve depressant in thetransdermal cream may be between approximately 0.1% and approximately5.0% of the total weight of the transdermal cream. Other amounts may beused.

The method 100 may comprise adding to the base composition a fine powderof medication that includes one or more muscle relaxants 110. The activeingredients that may be added to the base compositions in form of finepowder may comprise baclofen, carisoprodol, chlorzoxazone,cyclobenzaprine, dantrolene, diazepam, metaxalone, methocarbamol,orphenadrine, quinine sulfate, tizanidine, and/or other musclerelaxants. The low amount of muscle relaxant in the transdermal creammay be between approximately 0.1% and approximately 5.0% of the totalweight of the transdermal cream. Other amounts may be used.

The method 100 may comprise adding to the base composition a fine powderof medication that includes one or more NMDA receptor antagonists 112,such as ketamine. Ketamine may be useful because of its NMDA receptoractivity (antagonism). The low amount of NMDA receptor antagonist in thetransdermal cream may be between approximately 0.1% and approximately5.0% of the total weight of the transdermal cream. Other amounts may beused.

The method 100 may comprise adding to the base composition a fine powderof medication that includes one or more opiate or opioid agonists 114.C2 opiate agonists may include oxycodone, morphine, methadone,hydromorphone, and fentanyl. C3 opiate agonists may include hydrocodone,codeine, propoxyphene, butalbital, and pentazocine. The activeingredients that may be added to the base composition in the form offine powder may include the C2 and C3 opiate agonists named above and/ortramadol. The low amount of opiate or opioid agonist in the transdermalcream may be between approximately 0.1% and approximately 5.0% of thetotal weight of the transdermal cream. Other amounts may be used.

The method of compounding may also include addition of additionalcomponents such as solubility agents, emollients, emulsifiers, andpenetrant enhancers. For example, a thickening agent may be added toincrease a thickness or viscosity of the transdermal cream. In variousembodiments, the thickening agent may include gelling agents forexample. The thickening agent may include a polysaccharide or cellulosebased thickening agent. The thickening agent may be present in an amountbetween approximately 0.5% and approximately 10% by weight of thetransdermal cream. In one embodiment, the thickening agent is Krisgel100.

V. Another Exemplary Method of Compounding

A method of compounding medications with a transdermal cream using afine powder of medication is disclosed herein. In general, a basecomposition, such as a lidocaine/prilocaine cream, should be selected,such as lidocaine and prilocaine cream 2.5%/2.5%. The preparer, such asa pharmacist, should calculate the weight of powders needed. Then, theprepare should grind the medication in instances where powder medicationis to be obtained not from bulk or pure compounding powders but fromcommercial tablets, such as tablets formulated for oral administrationcontaining the medication, into fine powder and weigh the ingredients.The preparer should triturate the powders together and wet with dimethylsulfoxide (DMSO) or Sterile Water for Irrigation. The preparer maygenerally work the wetted powder into a paste. The preparer should bringto total weight with the lidocaine/prilocaine cream and mix well. In oneembodiment, the preparer may mix the paste and lidocaine/prilocainecream in a mixing bowl for 15 minutes on low. The mixture should bemilled in an ointment mill as necessary to acquire the desiredconsistency. The mill may be Exakt 120S-450 Three Roll Mill, frontroller “1”, rear roller “3”. After which, the preparer should mixthoroughly, e.g., on low for 15 minutes or as otherwise needed, andpackage appropriately.

More specifically, FIG. 2 depicts an exemplary method of compoundingmedications with a transdermal cream 200. The method 200 depicted inFIG. 2 may be used to manufacture the transdermal creams discussedherein, including those discussed in relation to FIG. 1 above. Themethod 200 may include selecting a base composition 202; calculating anamount of active ingredients 204; grinding up the tablets containing theactive ingredients 206; wetting the mixture with DMSO or Sterile Waterfor Irrigation 208; bringing to total weight 210; and milling in anointment mill and mixing 212. The method 200 may include additional,fewer, or alternate actions.

The method 200 may include selecting a base composition 202 for atransdermal cream or gel. The base composition may include one or morelocal anesthetics, such as lidocaine and/or prilocaine. The base mayinclude approximately equal amounts of lidocaine and prilocaine. Thebase composition may be a transdermal cream and may originally haveapproximately 2.5% lidocaine and approximately 2.5% prilocaine by weight(lidocaine and prilocaine cream (2.5%/2.5%)). Other initial amounts oflidocaine and/or prilocaine may be used. In one embodiment, the basecomposition that includes lidocaine and/or prilocaine may be used in anamount of approximately 24,000 gm. Other amounts of base composition maybe used.

The method 200 may include calculating an amount of active ingredients204. The active ingredients may come in various size tablets. Notedherein, one of the transdermal cream embodiments, includes meloxicam andlamotrigine. For that embodiment, the ingredients may include 15 mgtablets of meloxicam, and approximately 1,500 of the 15 mg tables ofmeloxicam may be used. Tablets with other dosages of meloxicam may beused, and in different amounts. For instance, 7.5 mg or 30 mg tablets ofmeloxicam may be used.

The ingredients may also include 200 mg tablets of lamotrigine, andapproximately 3,000 of the 200 mg tablets of lamotrigine may be used.Tablets with other dosages of lamotrigine may be used, and in differentamounts. For instance, lamotrigine tablets ranging from 2 to 200 mg maybe used.

To manufacture the transdermal cream embodiment that includes meloxicamand lamotrigine, the following formulas may be used to identify theamount of tablet powder of meloxicam and lamotrigine needed:

a. Meloxicam:

avg tab weight ______ gm×tablets needed ______=tablet powder needed______ gm.

b. Lamotrigine:

avg tab weight ______ gm×tablets needed ______=tablet powder needed______ gm.

The foregoing formulas may be used with the numbers stated above. Forinstance, the composition may require 1,500 of the 15 mg tables ofmeloxicam, and 3,000 of the 200 mg tablets of lamotrigine. As a result,in one embodiment, 22.5 grams of meloxicam and 600 grams of lamotriginemay be mixed with other ingredients, such as 24,000 gm of lidocaine2.5%/prilocaine 2.5% cream, as well as 2,550 gm of dimethyl sulfoxide(DMSO). Instead of or in addition to lamotrigine, the medications addedmay include topiramate or other active ingredients. Instead of DMSO,Sterile Water for Irrigation may be used.

The method 200 may comprise grinding up the tablets containing theactive ingredients 206. In one aspect, an automatic grinder may be usedto grind up tablets containing one or more active ingredients into finepowder of medication. For instance, a Grindomix Mill may be used havinga 100 volt, 60 Hz motor and five liter plastic container. The mill mayhave a standard lid, knife, and scraper. A five liter stainless steelcontainer may be used that includes a knife holder. A knife of stainlesssteel may be used, and be autoclavable. The mill may have a plasticcover that is transparent.

The grinding up of the active ingredients into fine powder may allow formore precise amounts of each active ingredient in the final transdermalcream. This may be especially important when adding low amounts ofactive ingredients such that the final transdermal cream has lowconcentrations of various medications, which may reduce adverse allergicreactions to prolonged usage.

The method may include wetting the mixture with DMSO or Sterile Waterfor Irrigation 208. The DMSO and/or Sterile Water for Irrigation mayfacilitate the active ingredients penetrating the skin. After theingredients in fine powder form are weighed, the preparer may trituratethe powders of each ingredient together and wet with DMSO. For the24,000 gm amount of lidocaine/prilocaine cream noted above, DMSO may beused in an amount of approximately 2,550 gm. Other amounts of DMSO maybe used.

Instead of DMSO, the method may include wetting the mixture with only orprimarily Sterile Water for Irrigation. Sterile Water for Irrigation USPmay be a sterile, hypotonic, nonpyrogenic irrigating fluid orpharmaceutic aid (solvent), and may be composed of Sterile Water forInjection USP. It may be prepared by distillation and may contain noantimicrobial or bacteriostatic agents or added buffers. The pH may beabout 5.7, or between 5.0 and 7.0. Sterile Water for Irrigation may beintended for use only as a single-dose, and may be classified as asterile irrigant, wash, rinse, diluent and pharmaceutical vehicle.Instead of or addition to Sterile Water for Irrigation, Sterile Waterfor Injection or purified water may be used.

The method may include bringing to total weight with thelidocaine/prilocaine cream and mixing well 210. As noted elsewhereherein, after the fine powder of medication is mixed with thelidocaine/prilocaine base, the final transdermal cream may haveapproximately 2.0% by weight lidocaine, approximately 2.0% by weightprilocaine, approximately 0.09% by weight meloxicam, and approximately2.5% by weight either lamotrigine or topiramate. The final transdermalcream may have other active ingredients as well, including thosementioned herein.

The method 200 may include milling the mixture in an ointment mill asnecessary to acquire the desired consistency 212. After which, thepreparer may mix the milled mixture thoroughly and package it inappropriate containers.

VI. Exemplary Storage Characteristics

The transdermal creams discussed herein that are made using fine powderof medication may exhibit excellent storage characteristics, and avoidseparation and/or degradation of the active ingredients from a basecomposition for substantial lengths of time, such as six months orgreater. For example, Table I below depicts the results of a 198 daypotency test for a transdermal cream including meloxicam, lamotrigine,lidocaine, and prilocaine. As shown, there is little degradation of theactive ingredients. The sample was stored in approximately 20° C. to 25°C. (68° F. to 77° F.) conditions, and contained one large white tubewith cream in a clear bag.

TABLE I 198 Day Potency Test Expected % Test Analyte/SpecificationsAmount Units Results of EXP. Method Lamotrigine 2.5 % 2.463 98.5% HPLCSpecifications = N/A Lidocaine 2.0 % 1.927 96.4% HPLC Specifications =N/A Meloxicam 0.09 % 0.0962 106.9% HPLC Specifications = N/A Prilocaine2.0 % 2.118 105.9% HPLC Specifications = N/A

Table II below depicts the results of a 100 day potency test for atransdermal cream including meloxicam, topiramate, lidocaine, andprilocaine. As shown, there is little degradation of the activeingredients. The sample was stored in approximately 20° C. to 25° C.(68° F. to 77° F.) conditions, and contained one large white tube withcream in a clear bag.

TABLE II 100 Day Potency Test Expected % Test Analyte/SpecificationsAmount Units Results of EXP. Method Lidocaine 2.0 % 1.700 85.0% HPLCSpecifications = N/A Meloxicam 0.09 % 0.0945 105.0% HPLC Specifications= N/A Prilocaine 2.0 % 1.899 95.0% HPLC Specifications = N/A Topiramate2.5 % 2.368 94.7% HPLC Specifications = N/A

VII. Exemplary Methods of Compounding Using Fine Powder

An exemplary method of compounding may include grinding up tablets ofone or more active ingredients into a fine powder, and then adding thoseingredients in powder form to a transdermal cream or gel. The activeingredients that are ground up into a fine powder of medication mayinclude one or more NSAIDs, anticonvulsants, nerve depressants, musclerelaxants, antidepressants, NMDA receptor antagonists, opioid or opiateagonists, local anesthetics, and/or other active agents. The transdermalcream or gel may or may not have one or more pre-existing ingredientsprior to the addition of the fine powder of medication, such as one ormore pre-existing local anesthetics.

The method may include grinding up tablets of one or more localanesthetics into a fine powder. The local anesthetics ground up intopowder form may include lidocaine and/or prilocaine, or other agents. Anamount of lidocaine and/or prilocaine powder may be added to thetransdermal cream such that lidocaine comprises between approximately0.5% and approximately 7.0% by weight of the transdermal cream, and thatprilocaine comprises between approximately 0.5% and approximately 7.0%by weight of the transdermal cream. Other amounts may be used, includingthose discussed elsewhere herein.

The method may include grinding up tablets of one or more NSAIDs into afine powder of medication. The NSAIDs that are ground up may includemeloxicam, fluribiprofen, nabumetone, and/or other NSAIDs. The amount ofNSAIDs may be between approximately 0.05% and 25.0% by weight of thetransdermal cream. For instance, the transdermal cream may includemeloxicam in a low amount of between approximately 0.05% andapproximately 0.15% by weight of the transdermal cream, and/orflurbiprofen or nabumetone in an amount between approximately 5.0% andapproximately 25.0% of the transdermal cream by weight. Other amountsmay be used, including those discussed elsewhere herein.

The method may include grinding up tablets of one or moreanticonvulsants into the fine powder of medication. The anticonvulsantsthat are ground up may include lamotrigine, topiramate, and/or otheranticonvulsants. The transdermal cream may include an amount ofanticonvulsant of between approximately 1.0% and approximately 5.0% byweight of the transdermal cream. Other amounts may be used, includingthose discussed elsewhere herein.

The method may include grinding up tablets of one or more musclerelaxants into a fine powder of medication. The muscle relaxants thatare ground up may include baclofen, cyclobenzaprine, and/or other musclerelaxants. The transdermal cream may include an amount of musclerelaxant of between approximately 1.0% and approximately 5.0% by weightof the transdermal cream. Other amounts may be used, including thosediscussed elsewhere herein.

The method may include grinding up tablets of one or more opioid oropiate agonists into a fine powder of medication. The opioid or opiateagonists that are ground up may include C2 or C3 opiate agonists,tramadol, and/or others. The transdermal cream may include an amount ofopioid or opiate agonist of between approximately 1.0% and approximately5.0% by weight of the transdermal cream. Other amounts may be used,including those discussed elsewhere herein.

The method may include grinding up tablets of one or more NMDA receptorantagonists into a fine powder of medication. The NMDA receptorantagonists that are ground up may be ketamine and/or other antagonists.The transdermal cream may include an amount of NMDA receptor antagonistof between approximately 1.0% and approximately 40.0% by weight of thetransdermal cream. Other amounts may be used, including those discussedelsewhere herein.

The method may include grinding up tablets of one or more nervedepressants into a fine powder of medication. The nerve depressants thatare ground up may include gabapentin and/or other nerve depressants. Thetransdermal cream may include an amount of nerve depressant of betweenapproximately 1.0% and approximately 15.0% by weight of the transdermalcream. Other amounts may be used, including those discussed elsewhereherein.

The method may include grinding up tablets of one or more tricyclicantidepressants or other antidepressants into a fine powder ofmedication. The tricyclic antidepressants that are ground up may includeamitriptyline and/or other antidepressants. The transdermal cream mayinclude an amount of antidepressant of between approximately 1.0% andapproximately 15.0% by weight of the transdermal cream. Other amountsmay be used, including those discussed elsewhere herein.

The fine powder of each active ingredient that is ground up may be addedto a transdermal cream or gel separately or collectively. Themedications may comprise approximately 20%, approximately 30%, orapproximately 40% or more of a transdermal cream by weight. Otheramounts may be used, including those discussed elsewhere herein.Alternatively, administering low doses or applying transdermal creams orgels with low concentrations of one or more active ingredients mayminimize adverse side effects, such as adverse skin conditions that maydevelop with usage. Therefore, the method may include adding severalmedications in fine powder form to a transdermal cream or gel toalleviate the magnitude of any adverse skin conditions that may arise,while simultaneously providing a compounded therapy.

In specific embodiments, the two or more medications that are ground upinto a fine powder may include (1) a NSAID (such as meloxicam) and ananticonvulsant (such as lamotrigine and/or topiramate); (2) a NSAID(such as fluribiprofen or nabumetone), a nerve depressant (such asgabapentin), and a muscle relaxant (such as baclofen orcyclobenzaprine); or (3) a NSAID (such as fluribiprofen or nabumetone),a nerve depressant (such as gabapentin), and an antidepressant (such asamitriptyline). Other combinations of medications may be used.

In one aspect, an amount of fine powder of several medications may beground up and then added to a transdermal cream or gel. The severalmedications may include: (1) at least one local anesthetic, such aslidocaine and/or prilocaine, in an amount between approximately 1.0% andapproximately 7.0% of the transdermal cream by weight; (2) at least onenerve depressant, such as gabapentin, in an amount between approximately5.0% and approximately 15.0% of the transdermal cream by weight; (3) atleast one NSAID, such as flurbiprofen or nabumetone, in an amountbetween approximately 5.0% and approximately 25.0% of the transdermalcream by weight; and/or (4) at least one muscle relaxant, suchcyclobenzaprine, in an amount between approximately 0.5% andapproximately 4.0% of the transdermal cream by weight such that multipleailments may be addressed simultaneously. In one embodiment, thetransdermal cream may comprise, by weight of the transdermal cream,approximately 2.0% lidocaine, approximately 2.0% prilocaine,approximately 6.0% gabapentin, approximately 1.0% cyclobenzaprine, andapproximately 10.0% flurbiprofen or approximately 20% nabumetone. Theseveral medications may also include an opioid or opiate agonist, atricyclic or other antidepressant, a NMDA receptor antagonist, and/orother active ingredients. In one embodiment, the transdermal creamincludes the NSAID nabumetone present in an amount approximately 10% byweight of the transdermal cream, the nerve depressant gabapentin presentin an amount approximately 6% by weight of the transdermal cream, andlidocaine and prilocaine each present in an amount approximately 1.5% byweight of the transdermal cream. The transdermal cream may also includeDMSO in an amount approximately 24% by weight of the transdermal cream.The lidocaine and prilocaine may be included in a base compositionhaving a higher percent composition of lidocaine and prilocaine byweight than after formulation into the transdermal cream with theadditional components. For example, a 100 gram batch of the compoundedtransdermal may include 60 grams of lidocaine and prilocaine cream(2.5%/2.5%) yielding approximately 1.5% of each lidocaine and prilocaineby weight of the transdermal cream. In another embodiment, thecompounded transdermal cream includes lidocaine and prilocaine eachpresent in an amount approximately 1.5% by weight of the transdermalcream, the tricyclic antidepressant amitriptyline in an amountapproximately 3% by weight of the transdermal cream, and the nervedepressant gabapentin present in an amount approximately 10% by weightof the transdermal cream. The transdermal cream may also include DMSO inan amount approximately 22% by weight of the transdermal cream. Thetransdermal cream may further include a thickening agent present in anamount between approximately 0.5% and approximately 10% (e.g., 5%) byweight of the transdermal cream. In one such embodiment, the thickeningagent is Krisgel 100 and is present in an amount approximately 5% byweight of the transdermal cream. The lidocaine and prilocaine may beincluded in a base composition having a higher percent composition oflidocaine and prilocaine by weight than after formulation into thetransdermal cream with the additional components. For example, a 100gram batch of the compounded transdermal may include 60 grams oflidocaine and prilocaine cream (2.5%/2.5%) yielding approximately 1.5%of each lidocaine and prilocaine by weight of the transdermal cream.

In another aspect, an amount of fine powder of several medications maybe ground up and then added to a transdermal cream or gel. The severalmedications may include: (1) at least one local anesthetic, such aslidocaine and/or prilocaine, in an amount between approximately 1.0% andapproximately 7.0% of the transdermal cream by weight; (2) at least onenerve depressant, such as gabapentin, in an amount between approximately5.0% and approximately 15.0% of the transdermal cream by weight; (3) atleast one NSAID, such as flurbiprofen or nabumetone, in an amountbetween approximately 5.0% and approximately 25.0% of the transdermalcream by weight; and/or (4) at least one tricyclic antidepressant, suchas amitriptyline, in an amount between approximately 0.5% andapproximately 4.0% of the transdermal cream by weight. In oneembodiment, the transdermal cream may comprise, by weight of thetransdermal cream, approximately 2.0% lidocaine, approximately 2.0%prilocaine, approximately 6.0% gabapentin, approximately 1.0%amitriptyline, and approximately 10.0% flurbiprofen or approximately20.0% nabumetone. The several medications may also include an opioid oropiate agonist, a muscle relaxant, a NMDA receptor antagonist, and/orother active ingredients.

In one embodiment, the lidocaine and prilocaine may each be present inan amount of approximately 1.5% by weight of the transdermal cream. Thenerve depressant may be gabapentin present in an amount approximately 6%by weight of the transdermal cream. The NSAID may be nabumetone presentin an amount approximately 10% by weight of the transdermal cream. Thetricyclic antidepressant may be amitriptyline present in an amountapproximately 2% by weight of the transdermal cream. The transdermalcream may also include DMSO in an amount approximately 20% by weight ofthe transdermal cream. The transdermal cream may further include athickening agent present in an amount between approximately 0.5% andapproximately 10% (e.g., 2%) by weight of the transdermal cream. In onesuch embodiment, the thickening agent is Krisgel 100 and is present inan amount approximately 2% by weight of the transdermal cream. Thelidocaine and prilocaine may be included in a base composition having ahigher percent composition of lidocaine and prilocaine by weight thanafter formulation into the transdermal cream with the additionalcomponents. For example, a 100 gram batch of the compounded transdermalmay include 60 grams of lidocaine and prilocaine cream (2.5%/2.5%)yielding approximately 1.5% of each lidocaine and prilocaine by weightof the transdermal cream.

In another aspect, an amount of fine powder of several medications maybe ground up and then added to a transdermal cream or gel. Thetransdermal cream may include lidocaine in an amount betweenapproximately 0.5% and approximately 7.0% by weight of the transdermalcream; prilocaine in an amount between approximately 0.5% andapproximately 7.0% by weight of the transdermal cream; meloxicam in anamount between approximately 0.01% and approximately 5.0% by weight ofthe transdermal cream; and lamotrigine and/or topiramate in an amountbetween approximately 0.5% and approximately 5.0% by weight of thetransdermal cream. In one embodiment, the transdermal cream may compriseapproximately 2.0% by weight of both lidocaine and prilocaine,approximately 0.09% by weight meloxicam, and approximately 2.5% byweight lamotrigine and/or topiramate. As a result, the transdermal creamor gel may allow for the topical administration of lidocaine,prilocaine, meloxicam, and lamotrigine and/or topiramate simultaneouslyduring use. The several medications may also include an opioid or opiateagonist, a muscle relaxant, a NMDA receptor antagonist, a nervedepressant, other NSAIDs, other anticonvulsants, and/or other activeagents, including those discussed elsewhere herein.

VIII. Additional Exemplary Embodiments

The present embodiments may include the presence of DMSO and/or SterileWater for Irrigation, such as DMSO or Sterile Water for Irrigation in asufficient quantity to allow for the topical delivery of the activeingredients mentioned herein. The transdermal cream of the presentembodiments may be compounded to have no bulk ingredients in it. Forinstance, during the methods discussed herein, the DMSO may be removedand replaced with Sterile Water for Irrigation. The transdermal creammay be DMSO-free.

In one aspect, compounded meloxicam, topiramate (and/or lamotrigine),lidocaine, and prilocaine cream may contain strictly commerciallyavailable medications. DMSO, which may be in some cream embodimentsdisclosed herein, may be replaced with Sterile Water for Irrigation.Sterile Water for Irrigation may act as a primary or sole penetrationenhancer in some embodiments.

Although experimentation and investigation continues, it is believedthat some detriments may develop from a transition to a DMSO-freecompounded transdermal cream. It is believed that the removal of DMSOfrom certain compounds may decrease the effectiveness of the compoundgiven that the primary penetrant is no longer present. Also, patientsthat have received the previous compounded version containing DMSO mayexperience lower efficacy rates. It is also believed that the transitionof the formula may, at best, give the same efficacy that the patientspreviously had experienced, and, at worst, decrease efficacy due to theabsence of DMSO.

On the other hand, the use of Sterile Water for Irrigation instead ofDMSO may be cheaper and involve an easier method of manufacture. Also,Sterile Water for Irrigation is an FDA-approved commercially availablemedication.

In one aspect, a transdermal cream that permits the simultaneousadministration of multiple medications in low concentrations may beprovided. The transdermal cream may include lidocaine in an amountbetween approximately 0.5% and approximately 7.0% by weight of thetransdermal cream; prilocaine in an amount between approximately 0.5%and approximately 7.0% by weight of the transdermal cream; meloxicam inan amount between approximately 0.01% and approximately 5.0% by weightof the transdermal cream; and lamotrigine in an amount betweenapproximately 0.5% and approximately 5.0% by weight of the transdermalcream. In one embodiment, the transdermal cream may compriseapproximately 2.0% by weight of both lidocaine and prilocaine,approximately 0.09% by weight meloxicam, and approximately 2.5% byweight lamotrigine. As a result, the transdermal cream may allow for thetopical administration of lidocaine, prilocaine, meloxicam, andlamotrigine simultaneously during use. The transdermal cream may furtherinclude only or primarily Sterile Water for Irrigation as a penetrationenhancer or other component, and be devoid of DMSO or DMSO-free.

In another aspect, a transdermal cream that permits the simultaneousadministration of multiple medications in low concentrations may beprovided. The transdermal cream may include lidocaine in an amountbetween approximately 0.5% and approximately 7.0% by weight of thetransdermal cream; prilocaine in an amount between approximately 0.5%and approximately 7.0% by weight of the transdermal cream; meloxicam inan amount between approximately 0.01% and approximately 5.0% by weightof the transdermal cream; and topiramate in an amount betweenapproximately 0.5% and approximately 5.0% by weight of the transdermalcream. In one embodiment, the transdermal cream may compriseapproximately 2.0% by weight of both lidocaine and prilocaine,approximately 0.09% by weight meloxicam, and approximately 2.5% byweight topiramate. As a result, the transdermal cream may allow for thetopical administration of lidocaine, prilocaine, meloxicam, andtopiramate simultaneously during use. The transdermal cream may furtherinclude only or primarily Sterile Water for Irrigation for penetrationenhancement or as a wetting component, and/or be devoid of DMSO orDMSO-free.

In another aspect, a method of compounding one or more medications witha transdermal cream for the topical administration of a compoundedtherapy may be provided. The method may include grinding up one or moretablets of a NSAID, an anticonvulsant, a nerve depressant, a musclerelaxant, a NMDA (N-Methyl-D-aspartate) receptor antagonist, an opiateor opioid agonist, and/or antidepressant into a fine powder ofmedication. The method may include wetting the fine powder of medicationmixture with DMSO or Sterile Water for Irrigation. The method may alsoinclude adding the fine powder of medication to a transdermal cream orbase composition containing both lidocaine and prilocaine, thetransdermal cream including both lidocaine and prilocaine in an amountof between approximately 0.5% and approximately 7.0% by weight of thetransdermal cream, respectively. The method may include adding the finepowder of compounded medication to the starting transdermal cream orbase composition in a sufficient amount such that the final transdermalcream includes the compounded medication that is ground up in a lowamount of between approximately 0.01% and approximately 5.0% by weightof the transdermal cream. In one embodiment, an amount of ground upmedication is added to the base composition such that the finaltransdermal cream contains low concentrations of several activeingredients and is approximately 2.0% by weight lidocaine, approximately2.0% by weight prilocaine, approximately 0.09% by weight meloxicam, andapproximately 2.5% by weight either lamotrigine or topiramate. In oneembodiment, the transdermal cream may further include only or primarilySterile Water for Irrigation for penetration enhancement or as a wettingcomponent, and/or be devoid of DMSO or DMSO-free.

In another aspect, a method of compounding medications with atransdermal cream for the topical administration of a compounded therapymay be provided. The method may include grinding up tablets of two ormore medications into a fine powder of compounded medication. The two ormore compounded medications to be ground up may be selected from aNSAID, an anticonvulsant, a nerve depressant, a muscle relaxant, a NMDAreceptor antagonist, a local anesthetic, an antidepressant, and anopioid or opiate agonist. The method may include wetting the fine powderof compounded medication with DMSO or Sterile Water for Irrigation. Themethod may include then adding the fine powder of compounded medicationto a transdermal cream or gel such that the transdermal cream or gelallows for topical delivery of the two or more compounded medicationsfor simultaneous treatment of two or more ailments when the transdermalcream or gel is topically applied. The transdermal cream may furtherinclude only or primarily Sterile Water for Irrigation for penetrationenhancement or as a wetting component, and/or be devoid of DMSO or otherpenetration enhancers.

The present invention may be embodied in other forms without departingfrom the spirit or essential attributes thereof and, accordingly,reference should be had to the following claims rather than theforegoing specification as indicating the scope of the invention.Further, the illustrations of arrangements described herein are intendedto provide a general understanding of the various embodiments, and theyare not intended to serve as a complete description. Many otherarrangements will be apparent to those of skill in the art uponreviewing the above description. Other arrangements may be utilized andderived therefrom, such that logical substitutions and changes may bemade without departing from the scope of this disclosure.

This disclosure is intended to cover any and all adaptations orvariations of various embodiments and arrangements of the invention.Combinations of the above arrangements, and other arrangements notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description. Therefore, it is intended thatthe disclosure not be limited to the particular arrangement(s) disclosedas the best mode contemplated for carrying out this invention, but thatthe invention will include all embodiments and arrangements fallingwithin the scope of the appended claims.

What is claimed:
 1. A compounded transdermal cream for the topicaladministration of a compounded therapy, the compounded transdermal creamcomprising: a nerve depressant in an amount between approximately 5% andapproximately 15% by weight of the transdermal cream, wherein the nervedepressant is gabapentin; an NSAID (Non-Steroidal Anti-InflammatoryDrug) in an amount between approximately 5% and approximately 25% byweight of the transdermal cream, wherein the NSAID is nabumetone; atricyclic antidepressant in an amount between approximately 0.5% andapproximately 4% by weight of the transdermal cream, wherein thetricyclic antidepressant is amitriptyline; a local anesthetic in anamount between approximately 1% and approximately 7% by weight of thetransdermal cream , wherein the local anesthetic comprises lidocaine andprilocaine; and dimethyl sulfoxide (DMSO).
 2. The compounded transdermalcream of claim 1, wherein the gabapentin is present in an amountapproximately 6% by weight of the transdermal cream, the nabumetone ispresent in an amount approximately 10% by weight of the transdermalcream, the amitriptyline is present in an amount approximately 2% byweight of the transdermal cream, and the lidocaine and prilocaine areeach present in an amount approximately 1.5% by weight of thetransdermal cream.
 3. The compounded transdermal cream of claim 2,wherein the DMSO is present in an amount approximately 20% by weight ofthe transdermal cream.
 4. The compounded transdermal cream 3, furthercomprising a thickening agent, wherein the thickening agent is presentin an amount approximately 2% by weight of the transdermal cream.
 5. Acompounded transdermal cream comprising: gabapentin in an amountapproximately 6% by weight of the transdermal cream; nabumetone in anamount approximately 10% by weight of the transdermal cream;amitriptyline in an amount approximately 2% by weight of the transdermalcream; lidocaine and prilocaine cream (2.5%/2.5%) in an amountapproximately 60% by weight of the transdermal cream such that thetransdermal cream comprises lidocaine in an amount approximately 1.5% byweight of the transdermal cream and prilocaine in an amountapproximately 1.5% by weight of the transdermal cream; dimethylsulfoxide (DMSO) in an amount approximately 20% by weight of thetransdermal cream; and a thickening agent in an amount approximately 2%by weight of the transdermal cream.
 6. A method of compounding atransdermal cream, the method comprising: wetting a plurality of drypowder active agents with dimethyl sulfoxide (DMSO), wherein the drypowder active agents comprise gabapentin, nabumetone, and amitriptyline;and mixing the wetted dry powder active agents with a lidocaine andprilocaine cream (2.5%/2.5%), wherein the gabapentin is present in thetransdermal cream in an amount between approximately 5.0% and 15.0% byweight of the transdermal cream, wherein nabumetone is present in thetransdermal cream in an amount of between approximately 5.0% andapproximately 25% by weight of the transdermal cream, and amitriptylineis present in an amount between approximately 0.5% and approximately4.0% by weight of the transdermal cream.
 7. The method of claim 6,wherein the dry powder active ingredients are gabapentin, nabumetone,and amitriptyline, and wherein the gabapentin is present in an amountapproximately 6% by weight of the transdermal cream, the nabumetone ispresent in an amount approximately 10% by weight of the transdermalcream, the amitriptyline is present in an amount approximately 3% byweight of the transdermal cream, and the lidocaine and prilocaine areeach present in an amount approximately 1.5% by weight of thetransdermal cream.
 8. The method of claim 7, wherein the DMSO is presentin an amount approximately 20% by weight of the transdermal cream. 9.The method of claim 8, further comprising adding a thickening agent tothe lidocaine and prilocaine cream (2.5%/2.5%) before or after mixingthe wetted dry powder active agents with the lidocaine and prilocainecream (2.5%/2.5%), wherein the thickening agent is present in an amountapproximately 2% by weight of the transdermal cream.